Alpha and Omega received mixed reviews from critics. The Rotten Tomatoes website said "With bland visuals and a dull, predictable plot, Alpha and Omega is a runt in 2010's animated litter." In Metacritic, the movie had a score of 37 out of 100, based on 15 critics. Some critics liked the voice performances by Justin Long and Hayden Panettiere. Other critics said it had a weak storyline, poor animation, and a predictable plot. In Amazon, Alpha and Omega received mostly positive reviews, for its animation, voice acting, characters and sense of humor.

Alpha and Omega didn't do well at the US box office. It grossed only $25 million. It did much better overseas, grossing $50 million on its $20 million budget. It was a commercial hit. This also made it the highest-grossing animated movie from Lionsgate.